Dataset Information

Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells.

ABSTRACT: Helicobacter pylori is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in H. pylori infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of H. pylori result from early phase and chronically activated pathways. In the present study we investigated the early host response to H. pylori in non-tumoral human gastric epithelial cells (GES-1). To dissect the pathogen-specific mechanisms we also examined the response to tumor necrosis factor (TNF), a prototypical cytokine. By analyzing the activation state of NF-κB signaling, cytokine expression and secretion, and the transcriptome, we found that the inflammatory response of GES-1 cells to H. pylori and TNF results from activation of multiple pathways and transcription factors, e.g., NF-κB and CCAAT/enhancer-binding proteins (CEBPs). By comparing the transcriptomic profiles, we found that H. pylori infection induces a less potent inflammatory response than TNF but affects gene transcription to a greater extent by specifically inducing transcription factors such as CEBPβ and numerous zinc finger proteins. Our study provides insights on the cellular pathways modulated by H. pylori in non-tumoral human gastric cells unveiling new potential targets.

SUBMITTER: Martinelli G

PROVIDER: S-EPMC10607124 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells.

Martinelli Giulia G Fumagalli Marco M Piazza Stefano S Maranta Nicole N Genova Francesca F Sperandeo Paola P Sangiovanni Enrico E Polissi Alessandra A Dell'Agli Mario M De Fabiani Emma E

International journal of molecular sciences 20231013 20

Helicobacter pylori is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in H. pylori infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of H. pylori result from early phase and chronically activated pathways. In the present study we investigated the ear ...[more]

PMID: 37894827

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Project description:Helicobacter pylori (H. pylori) are gram-negative bacteria that are able to colonize and persist in the stomach. Gastric cancer is tightly linked to chronic infection with this bacterium. Research over the last decades has illuminated the molecular interactions between H. pylori and host cells. It is now well established that H. pylori have multiple sophisticated means to adhere to epithelial cells and to manipulate their behavior. This interaction with the epithelium can lead to altered cell signaling, DNA damage and aberrant epithelial immunity. H. pylori are known to colonize the mucus layer of the stomach and surface epithelial cells. In addition, it has recently become clear that they can also penetrate the glands and directly interact with specialized epithelial cells deep in the glands. Understanding the biogeography of infection is important because gastric epithelial glands are composed of various types of short-lived differentiated cells that are constantly regenerated by a limited pool of long-lived stem cells located in base of gastric glands. Recent advances in gastric stem cell research not only led to identification of stem cell populations using specific markers but has also uncovered specific regulatory pathways and principles that govern gastric stem cell behavior and regeneration. Particularly, the stem cell state is largely dependent on signals from the niche cells that surround the stem cell compartment. The subpopulation of H. pylori that colonizes in the stem cell compartment triggers specific inflammatory responses and drives epithelial pathology. Colonization of gastric glands induces responses of the stem cell niche, simultaneously enhancing the cell turnover kinetics and driving the formation of antimicrobial cells in the gland base. These data reveal the high plasticity of the epithelium and its ability to adapt to the environment, which is necessary to regenerate and counterbalance infection, but simultaneously lays the grounds for development of gastric pathology and carcinogenesis.

Dataset Information

Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells.

Publications

Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and <i>Helicobacter pylori</i> Infection in Human Gastric Epithelial Cells.

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